318 
Monitoring Stem Cell Research 
cells. Other animal studies have shov\m contribution of bone marrow 
stem cells to repair of damaged renal tubules in the kidney;^^’®® taken 
together, animal studies indicate that bone marrow stem cells can 
participate in restoring damaged kidney tissue.®® 
Liver was one of the earliest tissues recognized as shovNhng 
potential contribution to differentiated cells by bone marrow stem 
cells. Bone marrow stem cells have been induced to form 
hepatocytes in culture®® and liver-specific gene expression has been 
induced in vitro in human bone marrow stem cells . In vivo, bone 
marrow stem cells were able to incorporate into liver as hepatocytes 
and rescue mice from a liver enzyme deficiency, restoring normal 
liver function.®^ Bone marrow stem cells also repopulated liver after 
irradiation of mice to destroy their bone marrow.®® Examination of 
livers of female patients who had received male bone marrow 
transplants, and male patients who had received female liver 
transplants, showed that similar repopulation of liver from bone 
marrow stem cells could take place in humans.®^ Examination of the 
kinetics of liver repopulation by bone marrow stem cells in a mouse 
model indicated that the replacement was slow, with only small 
numbers of cells replaced by the bone marrow stem cells.®® As noted 
previously, two recent studies have found that replenishment of liver 
by bone marrow stem cells occurs primarily via cell fusion hybrid 
formation, even in repair of liver damage.®® A side-population of stem 
cells has been identified in mouse liver, similar to that seen in bone 
marrow. This hepatic side-population, which contributes to liver 
regeneration, can be replenished by side-population bone marrow 
stem ceils.®® 
Pancreas and liver arise from adjacent endoderm during 
embryological development, and show relatedness in some gene 
expression and interconversion in some instances. Bone marrow 
derived cells have shown the ability to form pancreatic cells in 
animal studies. Mouse bone marrow stem cells containing a genetic 
fluorescent marker that is only expressed if insulin is expressed were 
transplanted into irradiated female mice.®^ Within 6 weeks of 
transplant, fluorescent donor cells were observed in pancreatic 
islets; donor cells identified in bone marrow eind peripheral blood did 
not show fluorescence. In vitro, the bone marrow derived cells 
showed glucose-dependent insulin secretion as well. Bone marrow 
derived stem cells have also demonstrated the ability to induce 
regeneration of damaged pancreas in the mouse.®® Mice with 
experimentally induced hyperglycemia from pancreatic damage were 
treated with bone marrow derived stem cells expressing the c-kit 
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